Renal cysts are central pathologic features of a number of congenital and acquired human disease states. Although thereby responsible for significant morbidity and mortality in both children and adults, the basic causes of renal cystic maldevelopment remain unknown. The current proposal is designed to study the pathogenesis of renal cyst formation in serum-free, murine metanephric organ culture models of normal, and cortisol-induced cystic, nephrogenesis. In the mode, fetal kidneys of Swiss-Webster albino mice undergo organotypic tubulogenesis and glomerulogenesis during 144 hours of in vitro incubation. This affords the opportunity to study the factors operative in cystic maldevelopment under highly controlled experimental conditions. An experimental hypothesis has been constructed to direct the studies of the current investigation. This hypothesis proposes that in metanephric organ culture, cortisol a) induces increases in metanephric Na-K-ATPase activity; b) that such increases in enzyme acitivity mediate altered transtubular transport of organic anions; and c) that increased transtubular transport of organic anions leads to net intratubular accumulation of solutes and fluid with resultant cystic tubular dilatation. To test each of the premises of the proposed hypothesis, the basic technique of organ culture will be utilized in concert with methods developed for enzyme-linked kinetic microassay of renal Na-K-ATPase, and measurement of radioisotopic uptake and autoradiographic localization of organic anions in metanephric microslices. These studies will identify independent cyst-promoting roles of cortisol, Na-K-ATPase activity, and organic anion transport, and characterize their interaction in mediating cyst formation in the metanephric organ culture model. The characterization of altered epithelial transport processes in organ culture cyst development may provide further insight into the complex pathogenesis of renal cyst production in human cystic disease states.